Platinum drugs are widely used in cancer therapy. Among the platinum drugs, cisplatin, carboplatin, and oxaliplatin have FDA approval and are clinically used in the United States and elsewhere. The use of platinum(II) drugs in the treatment of malignancies has been somewhat limited because of the side effects and resistance acquired by cancer cells. An alternative to platinum(II) drug candidates is the use of substitutionally more inert platinum(IV) compounds as prodrugs derived from clinically effective platinum(II) compounds. Substitutionally inert platinum(IV) complexes are less likely to be deactivated prior to reaching their destination target in the cancer cell. The activity of platinum(IV) complexes generally involves reduction with concomitant loss of the axial ligands, affording an active platinum(II) complex that readily binds to DNA. The axial ligands which are released from the platinum(IV) complex may comprise a therapeutically active agent.
It is known that cancer cells may have cellular pathways that differ from non-cancerous cells, which may be targeted by anticancer therapies. For example, it has been recently recognized that mitochondrion may be a target for anticancer therapy due to its role in arbitrating cell apoptosis.
Therefore, it would be beneficial to have methods and compositions for treating cancer using a dual mode therapy comprising a platinum drug and an agent which specifically affects a cellular pathway of a cancer cell.